1. Field of the Invention
The present invention relates to a process for preparing 2,2-difluoroethanol proceeding from 2,2-difluoro-1-chloroethane (1-chloro-2,2-difluorethane).
2. Description of Related Art
2,2-Difluoroethanol is an important intermediate in the synthesis of active agrochemical and pharmaceutical ingredients. There are various known processes for preparation of fluorinated alcohols. Many of the processes proceed via catalytic hydrogenation or through use of reducing agents.
Henne et al. describe, for example, in J. Am. Chem. Soc. 1952, 74, 1426-1428, the reduction of a difluoroacetyl chloride formed in situ by lithium aluminium hydride to obtain difluoroethanol in 69% yield. An economic disadvantage is the stoichiometric use of expensive hydride sources.
Booth et al. describe, in Tetrahedron 1990, 46, 2097-2110, the reduction of difluoroacetic acid with borane-dimethyl sulphide complex to obtain difluoroethanol in 55% yield.
EP-1 820 789 A1 describes the reduction of fluorinated carboxylic acids, carbonyl halides or carboxylic esters with hydrogen in the presence of a catalyst. The method described therein is said to be especially suitable for preparation of difluoroethanol (CF2HCH2OH), preferably proceeding from fluorinated esters, especially from methyl or ethyl difluoroacetate. The reaction takes place under elevated pressure, and the catalyst used is iridium, rhodium or ruthenium on charcoal. The publication states that, proceeding from methyl difluoroacetate, the desired difluoroethanol was obtained in a yield of 74.4% by catalytic hydrogenation using an Rh/C catalyst after 18 hours at 40 bar. One disadvantage of this process is the use of an expensive noble metal catalyst, and another is that the reaction is executed at high pressure, which has the consequence that the reaction has to be performed in specific high-pressure apparatuses.
WO 2007/071841, which is concerned with the preparation of difluoroethanol, uses, as the starting material for a (triple) catalytic hydrogenation, a compound CF2XC(O)X where Hal is Cl, Br or iodine (especially chlorodifluoroacetyl chloride). The catalysts used are especially ruthenium, rhodium, palladium, osmium, iridium and platinum, which have been applied to a support. The support should likewise have the function of a Lewis acid and especially contain aluminium ions (e.g. zeolites or montmorillonite). The reaction can take place in the gas phase, and in that case preferably at a temperature of 200 to 300° C. and a hydrogen pressure of preferably 1 to 5 bar. The reaction can likewise take place in the liquid phase, in which case the reaction temperature is between 40 and 70° C. The hydrogen pressure is preferably between 10 and 20 bar. The reaction in the gas phase is emphasised as advantageous since it gave better yields of difluoroethanol and a higher conversion rate.
WO 2009/040367 describes a process for preparing 2,2-difluoroethanol. For this purpose, in a first stage, 1-brom-2,2-difluoroethane is prepared proceeding from difluorovinylidene. In a second stage, the compound is reacted with an oxygen nucleophile, for example sodium or potassium salts of acetic or formic acid. WO 2009/040367 also states that the bromine atom in 1-bromo-2,2-difluoroethane is activated by reaction with magnesium, zinc, lithium or copper (especially NaI or KI) prior to reaction with the oxygen nucleophile.
More specifically, WO2009/040367 describes the preparation of difluoroethanol by, in stage 2, reacting difluorobromoethane with sodium acetate (=sodium salt of acetic acid) in the presence of potassium iodide, by heating to 130° C. in DMF for 18 h, followed by a base-catalysed transesterification in the presence of methanol. The difluoroethyl acetate formed can first be isolated by distillation in an intermediate step or converted directly to difluoroethanol. Proceeding from difluorobromoethane used, the yields are between 56.8 and 87%. The process described here is complex and relatively costly and requires many intermediate steps to arrive at the desired difluoroethanol. If only step 2 is to be performed, the expensive difluorobromoethane has to be purchased.
Japanese Publication JP 62-273925A (=JP 1987-273925A) describes the preparation of 2,2-difluoroethanol proceeding from 1-chloro-2,2-difluoroethane with butyrolactone in the presence of water and potassium hydroxide. For this purpose, the reaction mixture is heated to 200° C. in autoclave for 2.5 h, giving 2,2-difluoroethanol in only 48.6% yield at 86% conversion of the difluorochloroethane.
None of the aforementioned processes for preparation of 2,2-difluoroethanol are optimal. Many of the processes use expensive catalysts and it is necessary to work under pressure, which is always associated with a high level of complexity on the industrial scale. Other processes (for example that from WO 2009/040367) consist of several process steps, proceed via the expensive 1-bromodifluoroethane, which also has to be activated for better reaction, or use the cheaper 1-chloro-2,2-difluoroethane, in which the yield and selectivity of 48.6% achieved at 86% conversion of the difluorochloroethane is only very low, which is attributable to the use of the unreactive 1-chloro-2,2-difluoroethane.